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Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue–device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems. [ABSTRACT FROM AUTHOR]

Development of cardiac multiphysics models has progressed significantly over the decades and simulations combining multiple physics interactions have become increasingly common. In this review, we summarise the progress in this field focusing on various approaches of integrating ventricular structures. electrophysiological properties, myocardial mechanics, as well as incorporating blood hemodynamics and the circulatory system. Common coupling approaches are discussed and compared, including the advantages and shortcomings of each. Currently used strategies for patient-specific implementations are highlighted and potential future improvements considered. [ABSTRACT FROM AUTHOR]

Infarct extension involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ, eventually leading to heart failure. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. Using human patient‐specific left‐ventricular (LV) numerical simulations established from cardiac magnetic resonance imaging (MRI) of myocardial infarction (MI) patients, the correlation between infarct extension and regional mechanics abnormality was investigated by analysing the fibre stress–strain loops (FSSLs). FSSL abnormality was characterised using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. We found that infarct extension was correlated to severely abnormal FSSL in the form of counter‐clockwise loop at the RZ close to the infarct, as indicated by negative DREW values. In regions demonstrating negative DREW values, we observed substantial fibre stretching in the isovolumic relaxation (IVR) phase accompanied by a reduced rate of systolic shortening. Such stretching in IVR phase in part of the RZ was due to its inability to withstand the high LV pressure that was still present and possibly caused by regional myocardial stiffness inhomogeneity. Further analysis revealed that the occurrence of severely abnormal FSSL due to IVR fibre stretching near the RZ‐BZ boundary was due to a large amount of surrounding infarcted tissue, or an excessively stiff IZ. [ABSTRACT FROM AUTHOR]

The neural interface is a critical factor in governing efficient and safe charge transfer between a stimulating electrode and biological tissue. The interface plays a crucial role in the efficacy of electric stimulation in chronic implants and both electromechanical properties and biological properties shape this. In the case of cochlear implants, it has long been recognized that neurotrophins can stimulate growth of the target auditory nerve fibers into a favorable apposition with the electrode array, and recently such arrays have been re-purposed to enable electrotransfer (electroporation)-based neurotrophin gene augmentation to improve the "bionic ear." For both this acute bionic array-directed electroporation and for chronic conventional cochlear implant arrays, the electric fields generated in target tissue during pulse delivery are central to efficacy, but are challenging to map. We present a computational model for predicting electric fields generated by array-driven DNA electrotransfer in the cochlea. The anatomically realistic model geometry was reconstructed from magnetic resonance images of the guinea pig cochlea and an eight-channel electrode array embedded within this geometry. The model incorporates a description of both Faradaic and non-Faradaic mechanisms occurring at the electrode-electrolyte interface with frequency dependency optimized to match experimental impedance spectrometry measurements. Our simulations predict that a tandem electrode configuration with four ganged cathodes and four ganged anodes produces three to fourfold larger area in target tissue where the electric field is within the range for successful gene transfer compared to an alternate paired anode-cathode electrode configuration. These findings matched in vivo transfection efficacy of a green fluorescent protein (GFP) reporter following array-driven electrotransfer of the reporter-encoding plasmid DNA. This confirms utility of the developed model as a tool to optimize the safety and efficacy of electrotransfer protocols for delivery of neurotrophin growth factors, with the ultimate aim of using gene augmentation approaches to improve the characteristics of the electrode-neural interfaces in chronically implanted neurostimulation devices. [ABSTRACT FROM AUTHOR]

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored. [ABSTRACT FROM AUTHOR]

Computational models have become essential in predicting medical device efficacy prior to clinical studies. To investigate the performance of a left-ventricular assist device (LVAD), a fully-coupled cardiac fluid-electromechanics finite element model was developed, incorporating electrical activation, passive and active myocardial mechanics, as well as blood hemodynamics solved simultaneously in an idealized biventricular geometry. Electrical activation was initiated using a simplified Purkinje network with one-way coupling to the surrounding myocardium. Phenomenological action potential and excitation-contraction equations were adapted to trigger myocardial contraction. Action potential propagation was formulated within a material frame to emulate gap junction-controlled propagation, such that the activation sequence was independent of myocardial deformation. Passive cardiac mechanics were governed by a transverse isotropic hyperelastic constitutive formulation. Blood velocity and pressure were determined by the incompressible Navier-Stokes formulations with a closed-loop Windkessel circuit governing the circulatory load. To investigate heart-LVAD interaction, we reduced the left ventricular (LV) contraction stress to mimic a failing heart, and inserted a LVAD cannula at the LV apex with continuous flow governing the outflow rate. A proportional controller was implemented to determine the pump motor voltage whilst maintaining pump motor speed. Following LVAD insertion, the model revealed a change in the LV pressure-volume loop shape from rectangular to triangular. At higher pump speeds, aortic ejection ceased and the LV decompressed to smaller end diastolic volumes. After multiple cycles, the LV cavity gradually collapsed along with a drop in pump motor current. The model was therefore able to predict ventricular collapse, indicating its utility for future development of control algorithms and pre-clinical testing of LVADs to avoid LV collapse in recipients. [ABSTRACT FROM AUTHOR]

Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, leads to membrane potential depolarization, which increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In spiking neurons, it is activation of voltage-gated sodium channels (NaV channels) that leads to action potential generation. However, several other types of voltage-gated channels are expressed that also respond to electrical stimulation. In this study, we examine the response of voltage-gated potassium channels (KV channels) to brief electrical stimulation by whole cell patch-clamp electrophysiology and computational modeling. We show that nonspiking amacrine neurons of the retina exhibit a large variety of responses to stimulation, driven by different KV-channel subtypes. Computational modeling reveals substantial differences in the response of specific KV-channel subtypes that is dependent on channel kinetics. This suggests that the expression levels of different KV-channel subtypes in retinal neurons are a crucial predictor of the response that can be obtained. These data expand our knowledge of the mechanisms of neuronal activation and suggest that KV-channel expression is an important determinant of the sensitivity of neurons to electrical stimulation. NEW & NOTEWORTHY: This paper describes the response of various voltage-gated potassium channels (KV channels) to brief electrical stimulation, such as is applied during prosthetic electrical stimulation. We show that the pattern of response greatly varies between KV channel subtypes depending on activation and inactivation kinetics of each channel. Our data suggest that problems encountered when artificially stimulating neurons such as cessation in firing at high frequencies, or "fading," may be attributed to KV-channel activation. [ABSTRACT FROM AUTHOR]

Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Atrial Electrical Restitution Heterogeneity Introduction This study aims to characterize the regional variability in rate-adaptation in the atria. Methods and Results Action potential (AP) responses to pulses with uniform as well as pseudo-random non-uniform pacing intervals were recorded from rabbit sino-atrial node, right and left atrial pectinate as well as pulmonary vein antrum tissue preparations using conventional intracellular glass microelectrodes. Steady-state restitution curves were reconstructed for various AP waveform metrics. We observed significant variability between the four regions under basal pacing representing the rabbit resting heart rate as well as regional variability in rate-adaptation to increased pacing frequencies. Right-left atrial restitution differences were further confirmed using the non-uniform pacing protocol, with significant differences in AP amplitude, duration (APD) as well as maximum phase 0 depolarization rate restitution curves in response to an identical sequence of non-uniform pacing intervals. In addition, we report regional differences in alternans of AP waveform metrics, over a wide range of pacing frequencies and not simply prior to 1:1 entrainment being lost. We also observed an increase in APD90 along the conduction pathway from the left atrium to pulmonary vein junction. Conclusions Our results identified significant regional differences in electrical restitution in the rabbit atria and suggest their dependency on both baseline AP morphology and local intrinsic differences in rate-adaptation. We propose that the atrial heterogeneity in rate-adaptation could contribute to arrhythmogenesis and the greater susceptibility of pulmonary vein myocardial sleeves to ectopic foci and reentrant activity. [ABSTRACT FROM AUTHOR]

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis. Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall. [ABSTRACT FROM AUTHOR]

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented.Themodel provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. [ABSTRACT FROM AUTHOR]

In rat tail artery, activation of postjunctional α2-adrenoceptors by noradrenaline (NA) released from sympathetic axons produces a slow depolarization (NAD) of the smooth muscle through a decrease in K+ conductance. In this study we used intracellular recording to investigate whether the K+ channel involved is the ATP-sensitive K+ (KATP) channel. Changes in membrane resistance were monitored by measuring the time constant of decay of excitatory junction potentials. The KATP channel blockers, glibenclamide (10 μm) and PNU 37883A (5 μm), depolarized the smooth muscle and increased membrane resistance. Conversely, the KATP channel openers, pinacidil (0.1 and 0.5 μm) and levcromakalim (0.1 μm), hyperpolarized the smooth muscle and decreased membrane resistance. Activation of KATP channels with calcitonin gene-related peptide (CGRP; 10 nm) also hyperpolarized the smooth muscle and decreased membrane resistance. The NAD was abolished by both glibenclamide and PNU 37883A but was potentiated by CGRP. However, unlike CGRP, the directly acting KATP channel openers, pinacidil and levcromakalim, inhibited the NAD. The effects of other K+ channel blockers were also determined. A high concentration of Ba2+(1 mm), which would be expected to block KATP channels, abolished the NAD, whereas teteraethylammonium (1 mm) and 4-aminopyridine (1 mm) increased its amplitude. Apamin (0.5 μm) and a lower concentration of Ba2+ (0.1 mm) did not affect the NAD. These findings indicate that activation of α2-adrenoceptors by neurally released NA depolarizes the membrane of vascular smooth muscle by inhibiting KATP channels open in the resting membrane. [ABSTRACT FROM AUTHOR]

Flow energetics have been proposed as early indicators of progressive left ventricular (LV) functional impairment in patients with myocardial infarction (MI), but its correlation with individual MI parameters has not been fully explored. Using electro–fluid‐structure interaction LV models, this study investigated the correlation between four MI parameters: infarct size, infarct multiplicity, regional enhancement of contractility at the viable myocardium area (RECVM), and LV mechanical dyssynchrony (LVMD) with intraventricular vortex and flow energetics. In LV with small infarcts, our results showed that infarct appearance amplified the energy dissipation index (DI), where substantial viscous energy loss was observed in areas with high flow velocity and near the infarct‐vortex interface. The LV with small multiple infarcts and RECVM showed remarkable DI increment during systole and diastole. In correlation analysis, the systolic kinetic energy fluctuation index (E′) was positively related to ejection fraction (EF) (R2 = 0.982) but negatively correlated with diastolic E′ (R2 = 0.970). Diastolic E′ was inversely correlated with vortex kinetic energy (R2 = 0.960) and vortex depth (R2 = 0.876). We showed an excessive systolic DI could differentiate infarcted LV with normal EF from healthy LV. Strong flow acceleration, LVMD, and vortex‐infarct interactions were predominant factors that induced excessive DI in infarcted LVs. Instead of causing undesired flow turbulence, high systolic E′ suggested the existence of energetic flow acceleration, while high diastolic E′ implied an inefficient diastolic filling. Thus, systolic E′ is not a suitable early indicator for progressive LV dysfunction in MI patients, while diastolic E′ may be a useful index to indicate diastolic impairment in these patients. [ABSTRACT FROM AUTHOR]

This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed 'close-field electroporation'. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a 'humanized' neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies. • Cochlear mesenchymal cells can be targeted for gene electrotransfer via electric field compression using cochlear implants. • Regeneration of cochlear peripheral neurites after neurotrophin gene augmentation via bionic array-based electrotransfer. • Local recombinant neurotrophin expression enhances neural recruitment and electrically evoked auditory brainstem responses. • Bionic array directed gene electrotransfer requires low voltages albeit higher than existing cochlear implant capabilities. • Regulatory-permissive mini-plasmids free of antibiotic resistance genes achieve efficient gene expression in the cochlea. [ABSTRACT FROM AUTHOR]

Objective. A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced stimulation charge requirements. However, the performance of TIME, especially in the context of non-conventional stimulation waveforms, remains relatively unexplored. As part of our overarching goal of investigating stimulation efficacy of TIME, we developed a computational toolkit that automates the creation and usage of in silico nerve models with TIME setup, which solves nerve responses using cable equations and computes extracellular potentials using finite element method. Approach. We began by implementing a flexible and scalable Python/MATLAB-based toolkit for automatically creating models of nerve stimulation in the hybrid NEURON/COMSOL ecosystems. We then developed a sciatic nerve model containing 14 fascicles with 1,170 myelinated (A-type, 30%) and unmyelinated (C-type, 70%) fibers to study fiber responses over a variety of TIME arrangements (monopolar and hexapolar) and stimulation waveforms (kilohertz stimulation and cathodic ramp modulation). Main results. Our toolkit obviates the conventional need to re-create the same nerve in two disparate modeling environments and automates bi-directional transfer of results. Our population-based simulations suggested that kilohertz stimuli provide selective activation of targeted C fibers near the stimulating electrodes but also tended to activate non-targeted A fibers further away. However, C fiber selectivity can be enhanced by hexapolar TIME arrangements that confined the spatial extent of electrical stimuli. Improved upon prior findings, we devised a high-frequency waveform that incorporates cathodic DC ramp to completely remove undesirable onset responses. Conclusion. Our toolkit allows agile, iterative design cycles involving the nerve and TIME, while minimizing the potential operator errors during complex simulation. The nerve model created by our toolkit allowed us to study and optimize the design of next-generation intrafascicular implants for improved spatial and fiber-type selectivity., (Creative Commons Attribution license.)

Objective. Biomedical instrumentation and clinical systems for electrophysiology rely on electrodes and wires for sensing and transmission of bioelectric signals. However, this electronic approach constrains bandwidth, signal conditioning circuit designs, and the number of channels in invasive or miniature devices. This paper demonstrates an alternative approach using light to sense and transmit the electrophysiological signals. Approach. We develop a sensing, passive, fluorophore-free optrode based on the birefringence property of liquid crystals (LCs) operating at the microscale. Main results. We show that these optrodes can have the appropriate linearity ( µ ± s.d.: 99.4 ± 0.5%, n  = 11 devices), relative responsivity ( µ ± s.d.: 57 ± 12%V -1 , n  = 5 devices), and bandwidth ( µ ± s.d.: 11.1 ± 0.7 kHz, n  = 7 devices) for transducing electrophysiology signals into the optical domain. We report capture of rabbit cardiac sinoatrial electrograms and stimulus-evoked compound action potentials from the rabbit sciatic nerve. We also demonstrate miniaturisation potential by fabricating multi-optrode arrays, by developing a process that automatically matches each transducer element area with that of its corresponding biological interface. Significance. Our method of employing LCs to convert bioelectric signals into the optical domain will pave the way for the deployment of high-bandwidth optical telecommunications techniques in ultra-miniature clinical diagnostic and research laboratory neural and cardiac interfaces., (© 2022 IOP Publishing Ltd.)

In this research, a continuum multi-compartmental model of retinal electrical stimulation was utilized to find the best strategy for activating retinal ganglion cells (RGCs). Two types of return electrodes configuration placed suprachoroidally were used: monopolar and hexapolar. The current was delivered either simultaneously or sequentially with two kinds of waveforms: biphasic symmetric charge-balanced cathodic and anodic first pulses. Our results revealed there is no significant difference in current threshold between single monopolar and hexapolar stimulation regardless of the applied current stimulus waveform. Moreover, sequential stimulation for both monopolar or hexapolar was more effective in reducing current threshold than simultaneous stimulation when biphasic cathodic first pulses were used. Concurrent monopolar stimulation was significant in reducing the current threshold compared to single monopolar whereas concurrent hexapolar did not alter the current threshold. Overall, concurrent monopolar stimulation was efficacious in reducing current threshold regardless of the stimulus waveforms and sequential stimulation was more useful only with biphasic cathodic first pulses.

We propose an optical electrode 'optrode' sensor array for biopotential measurements. The transduction mechanism is based on deformed helix ferroelectric liquid crystals which realign, altering the optrode's light reflectance properties, relative to applied potential fields of biological cells and tissue. A computational model of extracellular potential recording by the optrode including the electro-optical transduction mechanism is presented, using a combination of time-domain and frequency-domain finite element analysis. Simulations indicate that the device has appropriate temporal response to faithfully transduce neuronal spikes, and spatial resolution to capture impulse propagation along a single neuron. These simulations contribute to the development of multi-channel optrode arrays for spatio-temporal mapping of electric events in excitable biological tissue.

We present a fully-coupled fluid-electromechanics model of the heart using a generic biventricular structure to provide a tool for future multiphysics interaction studies. A simplified Purkinje fibre structure was embedded within the myocardium along with transmural variation of action potential duration to obtain realistic activation and relaxation sequences. To ease computational requirements, phenomenological action potential and excitation-contraction formulations were chosen, and coupled to transverse isotropic hyperelastic myocardial material physics. The action potential propagation was discretised within the material frame to achieve electromechanical coupling with gap junction-controlled propagation. Blood haemodynamics was represented by incompressible Navier-Stokes equations, whereby, the endocardial displacement deforms the blood domain, whilst blood pressure and viscous stress exert load on the myocardium. Realistic electrical activation and relaxation sequences were achieved along with basic cardiac mechanical properties such as torsion and apex displacement. The pressure-volume loops for both ventricles matched known values, and vortex formation was noted during the filling phase. The model could facilitate a better understanding of multiphysics and biventricular interactions under pathologic conditions and help formulate better treatments.

The goal of this study was to develop an image-based model to computational investigate blood flow and pressure gradients resulting from left ventricular (LV) wall motion after the implantation of a mitral valve (MV) prosthesis. Two image-based 3D models were reconstructed from multi-slice computed tomography images obtained from patients undergoing transcatheter MV replacement. Navier-Stokes equations were then used to compute the fluid motion. Outflow tract obstruction of the models with MV prosthesis were identified by calculating the difference between LV systolic and aortic pressures. It was found that computed outflow track obstruction compared well with actual obstruction data obtained from two patients. Our study indicates computational modeling can be a valuable tool to investigate the optimal placement of prosthetic valves guided by individualized anatomical data.

A continuum multi-domain model of electrical stimulation of the retina is presented. Each point in the retinal ganglion cell layer could be thought of as representing a single cell, whose biophysics is described using a four-compartment formulation incorporating varying ion channel expressions in the soma, axon initial segment, dendrites and axon. Our continuum model was validated against a discrete morphologically-realistic OFF RGC model, using intra- and extra-cellular electrical stimulation scenarios. Simulations from the continuum model reproduced the same results as that of the discrete model. Our continuum model is the first multi-domain model to represent all main RGC compartments, not just the soma. Moreover, we demonstrated that this model allows the investigation of axonal activation which has been observed to influence the perception of phosphenes.

Multielectrode arrays (MEAs) are widely used for recording biopotentials, with an ongoing research effort to improve their characteristics and performance. In this spirit, we are currently investigating a novel concept for a liquid crystal-based optical electrode (optrode) that has the potential to overcome some of the limitations of MEAs, including that of wiring complexity. In this paper we present a model to fully describe the electrical response of the proposed optrode to biopotentials, taking into account dielectric relaxation. Since the frequency dependence of the complex permittivity is difficult to specify in time-stepped finite element (FE) simulations, where the implementation of time-convolution is nontrivial, we adopt an alternative approach to dielectric relaxation via the polarization vector. This approach, which is based on the Debye model, is then implemented in a FE model of the optrode. We show that the dielectric response of the liquid crystal layer has an effect on the complex signal behavior of the sensed biopotentials that must be taken into account when modeling the optrode.

Ventricular remodeling may occur following myocardial infarction of the left ventricle (LV) and such remodeling has been shown to be correlated with increased patient morbidity and mortality. It is thus important to estimate the likelihood of remodeling from the state of the infarcted LV. In this paper, we present simulations from an actively-contracting truncated ellipsoid LV model, incorporating realistic fiber orientation and electromechanical properties, to investigate the effects of infarct size and transmural extent (TME) on myofiber regional mechanics. Results showed that transmural infarcts greatly elevated both the myofiber stress and strain at the border zone during end systole, making the LV more susceptible to structural remodeling. It was found that TME rather than infarct size was more predictive of LV remodeling.

A novel computational modelling approach is employed to investigate the response of a population of retinal ganglion cells (RGCs) to external electrical stimulation. Current is delivered via a multi-electrode array design that would be employed in a future retinal prosthesis device being developed by our group. The RGCs are morphologically realistic and allow examination of the biophysical responses of intracellular compartments to externally applied currents. A number of stimulation paradigms are simulated including the use of monopolar, hexapolar and quasi-monopolar return paths. The model provides a powerful simulation tool to test and optimize electrical stimulation strategies for future retinal prosthesis devices.

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis. Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.

An isolated rabbit cardiac sinoatrial node (SAN) tissue preparation was used experimentally to map activation times and conduction velocities of extracellular cardiac action potential (AP) propagation. Extracellular recordings were carried out using a two-dimensional array of unipolar Ag-AgCl microelectrodes connected to a 128-channel data acquisition system. A 20(th) order, low-pass Butterworth filter, with a cut-off frequency of 50 Hz, was used in conjunction with a Matlab algorithm to map activation times and conduction velocities. Results show an initial slow-down of the activation wavefront emanating from the SAN, followed by acceleration in some regions, particularly near the Superior Vena Cava, as it travels towards the SAN periphery.

A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

Although significant advances have been made in continuum modeling of cardiac and smooth muscle tissue, the progress in neuronal continuum modeling has been slower. In this paper, a continuum neuronal tissue model based on a two-compartmental representation of cells is presented. Each neuron is described using both a somatic compartment modeled by the classical Hodgkin-Huxley current kinetics and a dendritic compartment based on a passive RC formulation. In addition, a synaptic current is fed into the dendritic compartment to account for the presynaptic influence of cells located within the dendritic field of each soma. A number of cases are simulated, including intracellular current injection into either the dendritic or somatic compartments, as well as extracellular current stimulation with and without synaptic input into neurons. The model incorporates a number of parameters controlling neuronal excitability which can be adjusted to validate each neuron's responses against experimental data, allowing for the modeling of different neuronal cell types and behaviors.

Computational models are valuable tools that can be used to aid the design and test the efficacy of electrical stimulation strategies in prosthetic vision devices. In continuum models of retinal electrophysiology, the effective extracellular potential can be considered as an approximate measure of the electrotonic loading a neuron's dendritic tree exerts on the soma. A convolution based method is presented to calculate the local spatial average of the effective extracellular loading in retinal ganglion cells (RGCs) in a continuum model of the retina which includes an active RGC tissue layer. The method can be used to study the effect of the dendritic tree size on the activation of RGCs by electrical stimulation using a hexagonal arrangement of electrodes (hexpolar) placed in the suprachoroidal space.

Generic ionic models optimized to replicate experimentally recorded cardiac action potentials (APs) from the central and peripheral sinoatrial node (SAN), the natural pacemaker of the heart, as well as atrial intact-myocytes are implemented in a realistic 2D model of rabbit SAN geometry. The model was used to investigate two frequently-proposed modes of SAN architecture: the gradient and mosaic hypotheses. In a simplified gradient arrangement, the peripheral SAN region acts as a transition zone between the central SAN and atrium and is required for spontaneous rhythmic initiation of APs from central SAN into the atria. Furthermore, the application of optimized single cell parameters to the realistic 2D rabbit geometry did not accurately replicate experimentally recorded APs. On the other hand, in an adapted mosaic geometry, peripheral SAN cells were not required to produce spontaneous regular excitation.

Despite reduced sympathetic activity below the level of a spinal cord injury (SCI), venoconstriction during autonomic dysreflexia increases venous return to the heart. Here, contractions of isometrically mounted tail veins from rats with spinal transection at T4 performed 8 - 10 weeks earlier are compared with those from sham-operated rats. After SCI, lumen diameter was reduced by ∼30% and the contractions evoked by electrical stimulation of the perivascular axons were larger than control. This augmentation of neurovascular transmission was not associated with enhanced sensitivity to α-adrenoceptor agonists or to adenosine-5'-triphosphate (ATP) although contractions to depolarization with K(+) were larger after SCI. The percentage reduction in nerve-evoked contraction after SCI produced by the α(1)-adrenoceptor antagonist prazosin (10 nM) was unchanged but that by the α(2)-adrenoceptor antagonist rauwolscine (0.1 μM) was reduced. The relative contribution of P2-purinoceptors to nerve-evoked contractions after α-adrenoceptor blockade, revealed by adding suramin (0.1 mM), was unchanged. The greater depolarization-induced contraction and the reduced contribution of α(2)-adrenoceptors to nerve-evoked contraction suggest that changes in the venous smooth muscle underlie the potentiation of neurovascular transmission after SCI. Furthermore, the smaller lumen diameter after SCI will increase the pressure that the veins exert on the luminal contents when they are neurally activated.

A cardiac sino-atrial tissue model based on a simplified 2D disc geometry and a generic ionic model is described and optimized to fit intact-tissue microelectrode experimental recordings. Concentric regions were defined representing the central and peripheral sino-atrial node and the atrium, each with a unique set of ionic model parameters. Intracellular action potentials were recorded from the respective myocytes in an intact rabbit in vitro sino-atrial tissue preparation. The 2D disc geometry was described numerically using a modified version of the cable equation of electrical propagation. The cell-specific model parameters at three nodes representing each region of the disc geometry were optimized, using a curvilinear gradient optimization algorithm, to generate action potentials waveforms that fitted the experimentally recorded waveforms. The optimized model was able to reproduce spontaneous sino-atrial node activation and atrial excitation and propagation. It offers an improved representation of the electrotonic interactions between heterogenous cell types and is able to reproduce the transition in action potential morphology between different regions. This tissue based optimization approach is a contribution to the development of realistic electro-anatomical cardiac models based on experimental data.